Tropical Medicine MS Thesis Defense, Natalie Subia: “”Dysregulation of complement components associated with inflammation and coagulation in virally suppressed people living with HIV”


10:00 AM - 11:00 AM


JABSOM Medical Education Bldg., Rm. 304
651 Ilalo St., Honolulu,, HI

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In Person & By Zoom

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Call in: (669) 900-6833
Zoom ID: 999 6612 8576
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Natalie Subia
M.S. Candidate
Department of Tropical Medicine, Medical Microbiology and Pharmacology
John A. Burns School of Medicine
University of Hawaiʻi at Mānoa

Although HIV has become a manageable chronic disease with the introduction of a combination of antiretroviral therapy, people living with HIV (PLWH) experience a high burden of age-related non-AIDS comorbidities (NACMs). PLWH often presents chronic inflammation and immune activation, which are thought to be key contributing factors for NACM development. The complement system is an essential component of the innate immune system that can influence HIV infection and replication. Although inappropriate or excessive complement activation contributes to various steps of an inflammatory response, little attention has been directed to determining its detrimental effects on the health conditions in virally suppressed PLWH. In this study, we found significant elevated C5a, but reduced C2 levels in the plasma samples from HIV-seropositive (HIV+) individuals, compared to HIV-seronegative (HIV-) individuals, but C3a and C9 levels were comparable between groups. Regardless of HIV-seropositive status, C2 levels were strongly associated with MPO, protein C, and ADAMST13, but C5a levels were associated only with protein C. However, the association trends ([C2, C5a, protein C, and MPO] and [MPO and ADAMST13]) were more robust in the HIV+ group than in the HIV- group. Although the percentages and counts of activated platelets (CD41+CD62P+ cells) were significantly reduced, the expression of CD62P on platelets was drastically increased in HIV+ individuals. Lastly, the treatment of plasma from HIV+ individuals to human neutrophils enhanced NETosis. However, plasma-induced NETosis was reduced, but non-lytic NET was still observed when platelets were removed. In summary, our study reports evidence of complement dysregulation associated with inflammation and coagulation in PLWH. In addition, altered systemic factors and elevated platelet activation in PLWH can trigger neutrophil activation and NET formation, leading to persistent inflammation, which is known as a major driver for developing NACMs.